Cell culture experiments validated the chronic endogenous replication stress in medulloblastoma cell lines and showed sharply differential, intriguing responses of normal cells and medulloblastoma cells to HCMV infection, including differential subcellular mislocalization and enhancement of replication stress‐related 53BP1 body formation, the latter in cell‐non‐autonomous manner. Here, TP53BP1 is linked to cytomegalovirus infection.